GLP-1 is an insulinotropic hormone secreted by the intestine that augments insulin secretion in response to food and lowers blood glucose in type 2 diabetics. As well as being insulinotropic, we proposed, based on in vitro work, that GLP-1 might also be insulinomimetic, i.e., it might also have some intrinsic glucose disposal properties similar to insulin. We are studying overweight individuals as they already have a reduction in insulin-mediated glucose disposal into tissues due to their obesity. We argued that if glucose disposal were already normal, then we might not see a difference in glucose disposal in the presence and absence of GLP-1. In normal-weight young men, indeed, we did not see a difference (JCEM 2399-2404, 1999). We are conducting the present study under conditions of euglycemia using glucose clamp technology. This involves two separate study days. The first study is performed with a primed continuous infusion of GLP-1 (1.5 pmol/kg min) from 0-60 minutes. At 60 minutes the GLP-1 infusion is terminated and euglycemia maintained from 60-120 minutes. Tritiated glucose is infused from -120 to +120 minutes in order to evaluate the contribution of the liver to glucose kinetics. After the GLP-1 study, each individual's plasma insulin levels are measured and a second study is done whereby insulin is infused in place of GLP-1 from 0-60 minutes to mimic the individual's insulin response to GLP-1 from the first study. The rate of disappearance (disposal) of glucose is then calculated for each individual under each study day. Any difference in disposal between the first and second study can then be attributed to GLP-1.